CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice.

Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in cystic fibrosis, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa, a pathogen that commonly colonizes and damages the lungs of patients with cystic fibrosis. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary P. aeruginosa infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact P. aeruginosa lung colonization, clearance, and the severity of the infection. These results also hold up in a cystic fibrosis mouse background, which has a hyperinflammatory immune response yet exhibits reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in cystic fibrosis. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.